Journal article
Intracranial mesenchymal tumor, FET::CREB fusion-positive: an integrative analysis of 81 cases
Neuro-oncology (Charlottesville, Va.)
01/22/2026
DOI: 10.1093/neuonc/noag001
PMID: 41569358
Abstract
Intracranial mesenchymal tumors, FET::CREB fusion-positive (ICMT), show fusions involving FET RNA-binding protein family genes (EWSR1 or FUS) and CREB family of transcription factors (ATF1, CREB1 or CREM). The methylation signature(s), gene expression characteristics and clinical behavior of this important tumor type require further characterization.
We study the methylation profiles of 81 ICMT cases (61 newly profiled cases and 20 cases from publicly available sources). Clinicopathologic and genomic data were recorded for each case when available.
ICMT showed a relatively distinct methylation signature compared to related tumors. Among the 65 cases where fusion types were documented, the identified fusions included EWSR1::ATF1 (25 cases), EWSR1::CREB1 (12 cases), EWSR1::CREM (21 cases), FUS::CREM (3 cases) and SMARCA2::CREM (4 cases). We confirmed the prior description of two distinct subgroups of ICMT (subclasses A and B). The majority of the cases belonged to subclass A (n = 69; 85%), which showed higher median age compared to subclass B patients (26 years vs. 15 years). Subclass B cases (n = 12; 15%) showed shorter progression-free survival (p < 0.01). Gene expression analysis of ICMT showed key overexpressed markers in ICMT, with significant CREM overexpression regardless of fusion type, when compared to either meningioma alone, or a larger group of CNS tumors.
This work provides further characterization of ICMT as an important CNS mesenchymal neoplasm that is prone to tumor recurrence, showing 2 prognostically relevant methylation subclasses, and warranting diagnostic distinction from other epigenetically and histologically related tumors. ICMTs show substantial overexpression of the CREM gene, independent of fusion type.
Details
- Title: Subtitle
- Intracranial mesenchymal tumor, FET::CREB fusion-positive: an integrative analysis of 81 cases
- Creators
- Sharika Rajan - National Cancer InstituteHye-Jung Chung - National Cancer InstituteZhichao Wu - National Cancer InstituteOmkar Singh - National Cancer InstituteKaren Dazelle - National Cancer InstituteZied Abdullaev - National Cancer InstituteManoj Tyagi - National Cancer InstituteChristina K Ferrone - National Cancer InstituteMark Raffeld - National Cancer InstituteIna Lee - National Cancer InstituteJeffrey Gagan - National Cancer InstituteJie Chen - University of Nebraska Medical CenterSahara Cathcart - University of Nebraska Medical CenterCaterina Giannini - Mayo ClinicAivi Nguyen - Mayo ClinicMurat Gokden - University of Arkansas for Medical SciencesArie Perry - University of California, San FranciscoIgor Lima Fernandes - Laboratório BacchiAngelica R Putnam - Primary Children's HospitalKyle Kurek - Primary Children's HospitalRichard M Green - Los Angeles Medical CenterCharles Eberhart - Johns Hopkins HospitalCalixto-Hope Lucas - Johns Hopkins HospitalIgnacio Gonzalez-Gomez - Johns Hopkins All Children's HospitalGiselle Yvette Lopez - Duke UniversityKarra Jones - Duke UniversityRichard Prayson - Cleveland ClinicGabrielle Yeaney - Cleveland ClinicJosephine Kam Tai Dermawan - Cleveland ClinicRati Chkheidze - University of Alabama at BirminghamChristina Appin - University of Alabama at BirminghamErik J Uhlmann - Beth Israel Deaconess Medical CenterAlisa Taliansky - Sheba Medical CenterMelissa Blessing - Texas Children's HospitalCarrie Mohila - Texas Children's HospitalJennifer Cotter - University of Southern CaliforniaJeremy Deisch - Loma Linda UniversityFelipe Andreiuolo - Department of Pathology, Rede D'Or, Rio de Janeiro, RJ, BrazilJohn R Crawford - Children's Hospital of Orange CountyChristopher Mount - Massachusetts General HospitalAnat O Stemmer-Rachamimov - Massachusetts General HospitalNelli S Lakis - The University of Kansas Health SystemRobert Schmidt - Washington University Medical CenterGeeta Chacko - Christian Medical College, VelloreRobert Newbury - Rady Children's Hospital-San DiegoStewart Neill - Emory University HospitalBryan Morales - Emory University HospitalRoger Fecher - Albert Einstein College of MedicineEmily A Sloan - Georgetown UniversityDavid A Solomon - Stanford MedicineMacLean Nasrallah - University of PennsylvaniaMartha Quezado - National Cancer InstituteAdriana Fonseca - Children's NationalKenneth Aldape - National Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Neuro-oncology (Charlottesville, Va.)
- DOI
- 10.1093/neuonc/noag001
- PMID
- 41569358
- NLM abbreviation
- Neuro Oncol
- ISSN
- 1523-5866
- eISSN
- 1523-5866
- Publisher
- Oxford University Press; CARY
- Grant note
- Intramural Research Program of the National Institutes of Health (NIH)National Institutes of Health (NIH)
Open Access funding is provided by the National Institutes of Health (NIH). This research was supported [in part] by the Intramural Research Program of the National Institutes of Health (NIH). The contributions of the NIH author(s) were made as part of their official duties as NIH federal employees, are in compliance with agency policy requirements, and are considered works of the United States Government. However, the findings and conclusions presented in this paper are those of the author(s) and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services.
- Language
- English
- Electronic publication date
- 01/22/2026
- Academic Unit
- Pathology
- Record Identifier
- 9985130056602771
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